7Z6E

Structure of the C1-PH-CNH regulatory module of MRCK1

Summary for 7Z6E

• Entry DOI: 10.2210/pdb7z6e/pdb
• Descriptor: Serine/threonine-protein kinase mrck-1, ZINC ION (3 entities in total)
• Functional Keywords: kinase, membrane, beta propeller, ph, lipid binding protein
• Biological source: Caenorhabditis elegans
• Total number of polymer chains: 5
• Total formula weight: 327403.29

Authors

Truebestein, L.,Leonard, T.A. (deposition date: 2022-03-11, release date: 2023-02-22, Last modification date: 2024-05-01)

Primary citation

Truebestein, L.,Antonioli, S.,Waltenberger, E.,Gehin, C.,Gavin, A.C.,Leonard, T.A.
Structure and regulation of the myotonic dystrophy kinase-related Cdc42-binding kinase.
Structure, 31:435-, 2023

PubMed Abstract: Protein kinases of the dystonia myotonica protein kinase (DMPK) family are critical regulators of actomyosin contractility in cells. The DMPK kinase MRCK1 is required for the activation of myosin, leading to the development of cortical tension, apical constriction, and early gastrulation. Here, we present the structure, conformation, and membrane-binding properties of Caenorhabditis elegans MRCK1. MRCK1 forms a homodimer with N-terminal kinase domains, a parallel coiled coil of 55 nm, and a C-terminal tripartite module of C1, pleckstrin homology (PH), and citron homology (CNH) domains. We report the high-resolution structure of the membrane-binding C1-PH-CNH module of MRCK1 and, using high-throughput and conventional liposome-binding assays, determine its binding to specific phospholipids. We further characterize the interaction of the C-terminal CRIB motif with Cdc42. The length of the coiled-coil domain of DMPK kinases is remarkably conserved over millions of years of evolution, suggesting that they may function as molecular rulers to position kinase activity at a fixed distance from the membrane.

PubMed: 36854301
DOI: 10.1016/j.str.2023.02.002

Experimental method

X-RAY DIFFRACTION (2.14 Å)